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Tree based orthology and paralogy determination: Phylogenetically inferred groups (PHIGS)

Abstract

The determination of orthology versus paralogy relationships amongst genes is of great importance to both comparative, functional and evolutionary genomics, as well as genome annotation. Our process involves hierarchical clustering of the genes from the available whole genome datasets such that gene clusters are consistent with the known evolutionary relationships of the organisms. For each cluster of genes that shares descent from a single common ancestor, a multiple sequence alignment and a maximum likelihood phylogenetic tree is created. By reconstructing the gene tree, not only can the tree be reconciled with the known evolutionary tree in order to identify orthology and paralogy relationships, but we also obtain a much more clear picture for rates of sequence change along the tree and potential positive selection across the lineages. In our process we are able to annotate genes using their evolutionary history instead of relying on similarity measures such as top or reciprocal best BLAST hits, which can be in error for genomes with large amounts of duplication or rate variation. We present results from clustering genes from over 30 Eukaryotic genomes as well as a significant number of Bacterial genomes. Additionally, we demonstrate the utility of this resource [http://PhIGs.jgi-psf.org] for transferring gene annotation from well annotated genomes to poorly annotated genomes, construction of phylogenetic trees and comparative genomics in general.

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